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Biomedical subjects

J De Groot

Publications and source records attributed to J De Groot.

9 recordsLinked to original sources

Carriers that concentrate native bone morphogenetic protein in vivo.

It is well known that the native bone morphogenetic protein (BMP) complex is much more active than each of its components: the concentration needed for extraskeletal bone induction is about a thousand times higher for a specific rhBMP than for the native BMP complex as a whole. Since the patient's own body is capable of producing the native BMP complex, the interesting question arises whether it is feasible to develop specific implants that concentrate native BMPs to levels that allow bone induction to take place. Such BMP-concentrating implants differ from carriers that are meant to passively store and deliver rhBMP. The fact that the native BMP complex is much more active than each of its constituent BMP molecules (the required concentration for the native complex is up to a thousand times lower) makes the question even more of interest. Based on the literature, the concept is developed in this article that selected implants, through mineralization in vivo, can concentrate the patient's own native BMP complex.

Animals↗

Reversal of mucosal tolerance by subcutaneous administration of interleukin-12 at the site of attempted sensitization.

Oral feeding of proteins causes peripheral T-cell tolerance, as revealed by reduced delayed-type hypersensitivity (DTH) reactivity after immunization. This type of tolerance can be due both to passive T-cell anergy and active immunosuppression. Using ovalbumin-fed mice we studied whether putatively immunostimulatory cytokines could break this state of mucosal tolerance. Cytokines were administered locally at the site of attempted sensitization. It was found that neither interleukin-2 (IL-2), interferon-gamma (IFN-gamma) nor granulocyte-macrophage colony-stimulating factor (GM-CSF) could restore the response to immunization. In contrast, local administration of IL-12 at the site of attempted immunization resulted in full recovery of DTH reactivity. The dichotomy between the two Th1 stimulatory cytokines IFN-gamma and IL-12 was also reflected by different effects on ovalbumin-specific antibody isotypes. Although both IFN-gamma and IL-12 downregulated serum IgG1-levels in tolerant mice, suggesting decreased ovalbumin-specific Th2 function, only local administration of IL-12 led to increased serum IgG2a levels. These results support the view that potentiation of Th1 effector function is critical for reversal of mucosal tolerance.

Animals↗

Peripolesis in alveolar sarcoidosis.

We observed that in bronchoalveolar lavages (BAL) of patients with active sarcoidosis (SARC) a mononuclear cell infiltrate is present that often contains clusters consisting of lymphocytes adhering to a macrophage. In order to investigate what kind of cellular interactions are involved in such a process, cell suspensions obtained from BAL of patients with SARC or extrinsic allergic alveolitis (EAA) were cultured for 1 to 2 days, during which time lapse cinematography was applied. We were able to show that such clusters consist of lymphocytes gathered around a macrophage. This is known as peripolesis. Peripolesis, as observed in our BAL, could last for some minutes or for some hours during which time a number of lymphocytes were moving around a single alveolar macrophage, without losing contact with the macrophage. Short interactions were mostly observed in EAA, whereas SARC was characterized by long periods of lymphocyte-macrophage cooperation. We also found a correlation between the time-dependent peripolesis t > 30 min/t < 30 min and the CD4/CD8 ratio. Although the precise mechanisms of peripolesis are not well understood, some interactions between lymphocytes and macrophages have now become more comprehensive.

Alveolitis, Extrinsic Allergic↗

MR imaging of cavernous sinus involvement by pituitary adenomas.

The ability of high-resolution MR imaging (1.5 T) to detect invasion of the cavernous sinuses by pituitary adenoma was determined through a retrospective review of 74 patients. These patients were divided into three groups: 25 normal subjects, 24 subjects with invasive pituitary adenomas, and 25 subjects with noninvasive pituitary adenomas. A fourth group of 30 patients, who subsequently underwent surgery for pituitary adenoma, was evaluated prospectively by MR for the presence or absence of cavernous sinus invasion. Several features were analyzed: (1) the detectability of the medial and lateral dural margins of the cavernous sinus (2) the size and variation in intensity of compartments within the cavernous sinus (3) the relationship of endocrine function to the surgical and MR appearance of the cavernous sinus and (4) carotid artery displacement or encasement by tumor. The normal cavernous sinuses were usually symmetric, but their sizes varied. The lateral dural margin of the cavernous sinus was always recognized on MR as a linear, discrete, low-intensity area. The medial dural margin (pituitary capsule) was seen on MR in only two of the 25 normal patients. In all 24 patients with cavernous sinus invasion involvement was unilateral and was most common with laterally positioned prolactin or adrenocorticotropic hormone secretory adenomas. Invasion of the cavernous sinus was suspected by MR in only two of the 13 invasive microadenomas and was questionable in three. In 10 of the 11 macroadenomas with surgically proved dural invasion, MR demonstrated an asymmetric increase in size and intensity of the superior and inferior cavernous sinus compartments. Noninvasive macroadenomas compressed and displaced the cavernous sinus bilaterally. The prospective MR evaluation of 30 patients undergoing surgery for pituitary tumor revealed a sensitivity for predicting cavernous sinus invasion of 55%, a specificity of 85.7%, a positive predictive value of 62.5%, and a negative predictive value of 81.8%. No feature permitted certain distinction between invasive and noninvasive microadenomas, as the medial dural wall of the cavernous sinus could not be reliably identified. The most specific sign of cavernous sinus invasion was carotid artery encasement.

Adenoma↗

CT-evaluation of extraocular muscles - anatomic-CT-correlations.

CT evaluation of the extraocular muscles is unsatisfactory in the commonly used axial and coronal planes. Based on the analysis of anatomic and computed tomographic sections and reformations in various planes, optimal examination techniques for the evaluation of the extraocular muscles are discussed. Their anatomic relationship to other clinically and surgically important orbital structures is shown. As a rule, visualization of an eye muscle is optimal if the plane of section or reformation is parallel to its course. Judgments regarding muscle size should be based only on true cross-sections obtained from reformations 90 degrees to the course of the individual muscle.

Diagnosis, Differential↗

In vivo imaging of the rat anatomy with nuclear magnetic resonance.

Live rats were imaged by nuclear magnetic resonance (NMR). These images demonstrated fine detail and high object contrast. Motion artifacts are not apparent in 4-minute images, and major blood vessels are demonstrated as regions of low signal intensity because of blood flow. Selective contrast enhancement is possible by varying NMR imager accumulation parameters.

Animals↗